US12161413B2 - Systems and methods for corneal property analysis using terahertz radiation - Google Patents
Systems and methods for corneal property analysis using terahertz radiation Download PDFInfo
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- US12161413B2 US12161413B2 US17/260,218 US201917260218A US12161413B2 US 12161413 B2 US12161413 B2 US 12161413B2 US 201917260218 A US201917260218 A US 201917260218A US 12161413 B2 US12161413 B2 US 12161413B2
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B3/00—Apparatus for testing the eyes; Instruments for examining the eyes
- A61B3/10—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions
- A61B3/107—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions for determining the shape or measuring the curvature of the cornea
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/05—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves
- A61B5/0507—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves using microwaves or terahertz waves
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- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
- G16H20/00—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance
- G16H20/40—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to mechanical, radiation or invasive therapies, e.g. surgery, laser therapy, dialysis or acupuncture
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- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
- G16H50/00—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics
- G16H50/30—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for calculating health indices; for individual health risk assessment
Definitions
- the present invention relates to corneal property analysis, and more particularly relates to systems and methods for corneal elasticity and/or rigidity analysis using terahertz (THz) time-domain spectroscopy.
- THz terahertz
- Ocular rigidity (OR) of eyeballs is affected not only by outer ocular coats (i.e. sclera and cornea), but also by the choroid and the status of ocular blood circulation.
- the rigidity may be altered by surgical procedures affecting the ocular walls, such as refractive procedures. Based on previous studies, the rigidity may, in turn, affect the accuracy of measurements of the intraocular pressure (IOP) as well as the pathogenesis of various ophthalmic conditions, such as glaucoma or age-related macular degeneration (AMD).
- IOP intraocular pressure
- AMD age-related macular degeneration
- a method for analysing a property of a cornea of an eye using terahertz (THz) radiation includes projecting a first THz wave onto a surface of the cornea and detecting a first reflected wave being a reflection of the first THz wave reflected from the surface of the cornea.
- the method further includes deforming the cornea, projecting a second THz wave onto the surface of the cornea after the deforming and detecting a second reflected wave being a reflection of the second THz wave reflected from the surface of the cornea after the deforming.
- the method includes calculating the property of the cornea based on the first reflected wave and the second reflected wave.
- a system for analysing a property of a cornea of an eye using terahertz (THz) radiation includes a device configured to deform the cornea, a terahertz radiation measuring system and a signal processing unit.
- the terahertz radiation measuring system includes a terahertz radiation generator and a terahertz radiation detector.
- the terahertz radiation generator is configured to project a first THz wave and a second THz wave respectively before and after the corneal deforming.
- the terahertz radiation detector is configured to detect a first reflected wave being a reflection of the first THz wave reflected from the surface of the cornea and detect a second reflected wave being a reflection of the second THz wave reflected from the surface of the cornea after the deforming.
- the signal processing unit is configured to communicate with the terahertz radiation measuring system to calculate the property of the cornea based on the first reflected wave and the second reflected wave.
- a computer readable medium providing instructions for a system to perform a method for analysing a property of a cornea of an eye using terahertz (THz) radiation.
- the computer readable medium includes instructions for the system to project a first THz wave onto a surface of the cornea and detect a first reflected wave being a reflection of the first THz wave reflected from the surface of the cornea.
- the computer readable medium further includes instructions for the system to deform the cornea, project a second THz wave onto the surface of the cornea after the deforming and detect a second reflected wave being a reflection of the second THz wave reflected from the surface of the cornea after the deforming.
- the computer readable medium includes instructions for the system to calculate the property of the cornea based on the first reflected wave and the second reflected wave.
- FIG. 1 depicts an illustration of a system for analysing properties of a cornea of an eye using terahertz (THz) radiation in accordance with present embodiments.
- THz terahertz
- FIG. 2 depicts an illustration of the system of FIG. 1 including a light stress device for performing corneal property analysis in accordance with the present embodiments.
- FIG. 3 depicts a flow chart of a method for analysing corneal properties of an eye using terahertz radiation in accordance with the present embodiments.
- FIG. 4 depicts a schematic diagram for operation of the system of FIG. 2 in accordance with the present embodiments.
- FIG. 5 depicts a graph of results of corneal property measurements for a light stressed porcine eye in accordance with the present embodiments.
- FIG. 6 depicts a graph of terahertz signals of two porcine eye samples measured in accordance with the present embodiments.
- terahertz terahertz
- Rigidity describes the mathematical relationship between the volume tended by a confined structure filled with incompressible contents such as fluid and the pressure inside the structure. Thus, rigidity reflects the elastic properties of the structure walls.
- ocular rigidity OR
- OR ocular rigidity
- OR may be altered by surgical procedures affecting the ocular walls such as refractive surgical procedures.
- OR may affect accuracy of intraocular pressure and pathogenesis of various ophthalmic conditions such as glaucoma or age-related macular degeneration.
- Axial length-associated OR measurement measures ocular axial length changes induced by, for example, oral administration of acetazolamide with partial coherence laser interferometry.
- the acetazolamide reduces the intraocular pressure and this pressure reduction can be measured with dynamic contour tonometry before and about two hours after the acetazolamide intake.
- the resulting axial length decrease per intraocular pressure reduction is then used to estimate ocular rigidity, however this measurement process over two hours takes a long time and results in significant patient suffering.
- Corneal hysteresis measured with an ocular response analyzer, such as an ORA, manufactured by Reichert Inc. of Buffalo, NY, USA, reflects viscous damping in the cornea (i.e., the capacity of corneal tissue to recover their shape following application of external forces).
- the ocular response analyzer releases a precisely metered air pulse that causes the cornea to move inward, the air pulse successively passing inward through the cornea and then outward.
- Fundus Pulse Amplitude and Ocular Pulse Amplitude measurement of corneal hysteresis process is intrusive and takes a long time, causing patients and ophthalmologists inconvenience.
- Embodiments of systems and methods of the present invention operate in the THz range in the electromagnetic spectrum which lies between microwave and infrared frequencies and generally defines frequencies ranging from 100 GHz (10 11 Hz, 3 mm wavelength) to 10 THz (10 13 Hz, 3.3 ⁇ m wavelength). Electromagnetic radiation in the THz range may also be referred to as THz light, THz radiation, or THz waveforms.
- a system such as a terahertz portable system, analyses corneal elasticity and rigidity ex-vivo and in-vivo using terahertz time-domain spectroscopy.
- a system for analysing corneal elasticity and rigidity of an eye using terahertz (THz) radiation uses a THz time-domain (THz-TDS) system 102 , a computer or other processing means 104 .
- THz-TDS THz time-domain
- the THz-TDS system 102 can be configured to reflect electromagnetic radiation 110 in THz range from a THz transmitter or emitter 112 toward a surface of an eye 114 , receive THz light reflected from the eye at a THz detector or receiver 116 , and generate a signal 118 indicative of the received radiation which is amplified and digitized by circuitry 120 .
- the THz radiation is generated by the THz transmitter 112 , such as an antenna or a nonlinear crystal, and pulsed in response to a signal from a femtosecond laser 122 .
- the THz detector or receiver 116 can also be an antenna or a nonlinear crystal.
- the computer 104 which communicates with THz-TDS system 102 , can be configured to process the generated signal 118 and may further be configured for creating a visual imaging of the THz response from the surface of the eye 114 .
- a XYZ stage 105 can be configured to manipulate the structure of the THz-TDS system 102 to scan the surface of the eye 114 and move THz focal point 124 from a surface of the eye 114 to a level below the surface of the eye.
- the system 100 for corneal rigidity and elastic analysis includes an illumination system (e.g., the femtosecond laser 122 and the THz transmitter 112 ) configured to provide an illumination beam of terahertz radiation 110 , an optical system including mirrors and lenses (e.g., lens 113 ) arranged in an optical path of the terahertz radiation 110 to relay and direct at least a portion of the illumination beam of terahertz radiation 110 onto a cornea 114 of a subject and to receive at least a portion of terahertz radiation reflected from said cornea to provide a return beam of terahertz radiation, and a detection system (e.g., detector 116 ) arranged in an optical path of said return beam of terahertz radiation, the detection system configured to provide a detection signal 118 from detecting at least a portion of said return beam of terahertz radiation.
- a signal processing system 120 is configured to communicate with the detection system 116 to receive the detection signal 118 , wherein the signal processing system processes
- the illumination system comprises a THz generator head including the femtosecond laser 122 and a nonlinear optical crystal (i.e., the THz transmitter 112 - 112 ).
- the optical system is configured to focus oblique-angle illumination of terahertz radiation on the subject's cornea 114 at the focal point 124 .
- the illumination optical system which can be open space or fiber connected, includes a pair of off-axis parabolic mirrors 126 , 128 and a pick-up optical system configured to provide the return beam of terahertz radiation also includes a pair of off-axis parabolic mirrors 130 , 132 .
- the detection system 116 is configured to detect said return beam of terahertz radiation within a frequency band of about 0.1 THz to about 10 THz.
- One of objectives of the present embodiments is to provide a non-contact system for measuring corneal mechanical properties and a method for measuring corneal elasticity.
- an illustration 200 depicts use of the system 100 and a light stress device 202 for performing corneal property analysis of a subject's eye 204 in accordance with the present embodiments.
- the present embodiments provide a non-contact system for measuring corneal mechanical properties of the subject's eye 204 , which includes a light-pressure device 202 , which provide a light toward a cornea of a live eyeball from about a distance of one or two centimeters in front of the eyeball and measures light pressure thereof.
- the light-pressure device 202 is configured to deform the cornea, preferably for less than ten seconds, and can be a red light having a wavelength of 632 nm generated by the light-pressure device at a power of 100 ⁇ W. Another corneal deformation device could also be used, such as an air-puffing device.
- the terahertz radiation measuring system includes the THz wave generator 112 and the THz detector 116 and generates terahertz radiation before and after the light-pressure device 202 applies stress on the surface of cornea for measuring corneal deformation caused by the light applied to the cornea.
- the signal processing unit 120 including computer 206 which controls the system by, for example, synchronizing operation of the light-pressure device 202 and the terahertz radiation measuring system (THz-TDS), as well as calculating the elastic constant by utilizing the corneal deformation measured by the terahertz radiation and the measured light pressure.
- THz-TDS terahertz radiation measuring system
- x can be derived from the THz peak position change before and after a visible light beam is shined on the cornea to provide stress
- F the light pressure (i.e., stress) given by the visible light as seen in Equation (3).
- F (1+ p ) E/C (3) where p is reflection coefficient, E is incident energy flux in W/m 2 , and C is the speed of light in a vacuum.
- Equation (2) c represents a spring constant, and once force F and deformation x are confirmed, then c can be calculated. More properties can be added for Equation (2) for more complex systems, which is closer to a real system as shown in Equation (4).
- F cx+nx′+mx′′ (4) where n represents a damping factor and m represents mass.
- This technology can be useful in patients who are undergoing laser refractive surgery. Monitoring of the corneal components during refractive surgery to adjust the femtosecond laser operating conditions can improve the successful rate of the operations. With current refractive surgery, the only parameter which is not precisely accessed is the cornea rigidity, which is believed to be the affecting factor for the current gap. With the present technology developed, the cornea properties, stromal components concentration, corneal elastic/rigidity etc.; can be instantly measured as the input for the laser operation conditions.
- This technology can also be useful for the patients with dry eyes.
- the doctors could monitor the tear film performance, therapeutic response and analysis the dry eye formation.
- the technology is useful in patients with corneal edema from infections or other degenerative conditions and can contribute to the early diagnosis, treatment and monitoring of various corneal diseases.
- the present invention is able to observe dynamic behaviour of the corneal which shows the dynamic changes of the corneal after the stress. From the THz spectroscopy, the present invention is able to continuously observe the dynamic changes of the corneal or even observe the recovery of the corneal after the stress.
- the information obtained could help in the design of non-invasive cornea elastic and ocular rigidity (OR) measurement modalities, such as ophthalmic elastography systems, applicable in the everyday clinical practice, which could be used in the study of a variety of ophthalmic conditions, including glaucoma, age-related macular degeneration, changes induced in the eye by refractive surgery as well as in the study for presbyopia.
- OR cornea elastic and ocular rigidity
- the graph 500 depicts results of corneal property measurements for a light stressed porcine eye in accordance with the present embodiments.
- the THz signal amplitude is measured along the y-axis 502 while the optical delay is measured along the x-axis 504 .
- the THz signal is been collected on the surface of the corneal without light.
- the time delay of THz signal shifts instantly, indicating deformation of the cornea.
- the difference between the curves with no light stress and the 1st curve collected immediately after the light source is off is due to the corneal deformation induced by the light stress.
- the cornea elastic/rigidity properties can be determined.
- a graph 600 depicts terahertz signals of two porcine eye samples 602 , 604 measured to show the THz signals comparison before and after light stress in accordance with the present embodiments.
- the two porcine eye samples 602 , 604 demonstrate different THz displacement under the same light stress.
- the recovering speed also shows the measurable difference.
- the present embodiments provide a method for analysing a property of a cornea of an eye using terahertz (THz) radiation by projecting a first THz wave onto a surface of the cornea and detecting a first reflected wave being a reflection of the first THz wave reflected from the surface of the cornea.
- the cornea is then deformed, a second THz wave onto the surface of the cornea after the deforming and the second reflected wave being a reflection of the second THz wave reflected from the surface of the cornea is detected after the deforming.
- the properties of the cornea are then calculated based on the first reflected wave and the second reflected wave.
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Abstract
Description
E=2G(1+v) (1)
wherein v represents a number called Poisson's ratio. The properties of the cornea such as elasticity are derived from a force-motion relationship as shown in Equation (2).
F=cx (2)
F=(1+p)E/C (3)
where p is reflection coefficient, E is incident energy flux in W/m2, and C is the speed of light in a vacuum.
F=cx+nx′+mx″ (4)
where n represents a damping factor and m represents mass.
F=cx (5)
where x is derived from a peak position change in the first reflected wave and the second reflected wave and F is the light stress induced by the visible light, F being calculated by Equation (6):
F=(1+p)E/C (6)
where p is a reflection coefficient of the surface of the cornea, E is incident energy flux of the visible light in W/m2 and C is the speed of light in a vacuum. Calculating the property of the cornea can also include calculating an elastic property, c, of the cornea based on Equation (7):
F=cx+nx′+mx″ (7)
where x is derived from a peak position change in the first reflected wave and the second reflected wave, F is the light stress induced by the visible light, n is a damping factor of the cornea, m is the mass of the cornea, x′ is a first order derivative of x, and x″ is a second order derivative of x, where F is calculated by Equation (7). The step of calculating the property of the cornea may also include calculating a rigidity property, G, of the cornea based on Equation (8):
c=2G(1+v) (8)
where c is the elastic property of the cornea, and v represents a Poisson's ratio of the cornea.
x=C×(t2−t1) (9)
Claims (22)
F=cx (1),
F=(1+p)E/C (2),
c=2G(1+v) (5),
x=C×(t2−t1) (6),
F=cx+nx′+mx″ (3),
F=(1+p)E/C (4),
F=cx (1),
F=(1+p)E/C (2),
c=2G(1+v) (5),
x=C×(t2−t1) (6),
F=cx+nx′+mx″ (3),
F=(1+p)E/C (4),
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| Application Number | Priority Date | Filing Date | Title |
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| SG10201806046S | 2018-07-13 | ||
| SG10201806046S | 2018-07-13 | ||
| PCT/SG2019/050337 WO2020013762A1 (en) | 2018-07-13 | 2019-07-10 | Systems and methods for corneal property analysis using terahertz radiation |
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| US20210298594A1 US20210298594A1 (en) | 2021-09-30 |
| US12161413B2 true US12161413B2 (en) | 2024-12-10 |
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| Country | Link |
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| US (1) | US12161413B2 (en) |
| SG (1) | SG11202100380PA (en) |
| WO (1) | WO2020013762A1 (en) |
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| TR2021002360A2 (en) * | 2021-02-19 | 2022-08-22 | Bursa Teknik Ueniversitesi Rektoerluegue | Adulteration and authenticity analysis method of organic substances and materials by terahertz spectroscopy |
| CN116725475B (en) * | 2023-05-15 | 2024-03-12 | 北京大学 | Measurement system and method for biomechanical properties of cornea |
| CN117563147B (en) * | 2023-12-12 | 2024-06-04 | 天津大学四川创新研究院 | Portable small living animal eye terahertz radiation device and experimental method |
Citations (3)
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|---|---|---|---|---|
| US5636635A (en) * | 1991-10-10 | 1997-06-10 | Massie Research Laboratories, Inc. | Non-contact tonometer |
| US7641343B1 (en) * | 2007-07-26 | 2010-01-05 | Motamedi Manouchehr E | Method and apparatus for early diagnosis of Alzheimer's using non-invasive eye tomography by terahertz |
| US20120265047A1 (en) | 2011-04-14 | 2012-10-18 | Crystalvue Medical Corporation | Intraocular pressure detecting device and detecting method thereof |
-
2019
- 2019-07-10 WO PCT/SG2019/050337 patent/WO2020013762A1/en not_active Ceased
- 2019-07-10 US US17/260,218 patent/US12161413B2/en active Active
- 2019-07-10 SG SG11202100380PA patent/SG11202100380PA/en unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5636635A (en) * | 1991-10-10 | 1997-06-10 | Massie Research Laboratories, Inc. | Non-contact tonometer |
| US7641343B1 (en) * | 2007-07-26 | 2010-01-05 | Motamedi Manouchehr E | Method and apparatus for early diagnosis of Alzheimer's using non-invasive eye tomography by terahertz |
| US20120265047A1 (en) | 2011-04-14 | 2012-10-18 | Crystalvue Medical Corporation | Intraocular pressure detecting device and detecting method thereof |
Non-Patent Citations (9)
| Title |
|---|
| Correas-Serrano, Diego, and J. Sebastian Gomez-Diaz. "Graphene-based antennas for terahertz systems: a review." arXiv preprint arXiv: 1704.00371 (2017) (Year: 2017). * |
| Dorronsoro et al., "Dynamic OCT measurement of corneal deformation by an air puff in normal and cross-linked corneas," Biomedical Optics Express, Feb. 9, 2012, vol. 3, No. 3, pages e473: 1-15 [Retrieved on Aug. 19, 2019] <DOI: 10.1364/BOE.3.000473> whole document. |
| International Preliminary Report on Patentablity from Singapore International Application No. PCT/SG2019/050337, issued Jan. 19, 2021, 4 pages. |
| International Search Report from Singapore International Application No. PCT/SG2019/050337, mailed Feb. 9, 2019, 3 pages. |
| Sung, Shijun, et al. "Direct measurement of corneal tissue water content by reflection imaging at Terahertz Frequencies." Investigative Ophthalmology & Visual Science 56.7 (2015): 1644-1644. (Year: 2015). * |
| Taylor et al., "THz Medical Imaging: in vivo Hydration Sensing," IEEE Trans Terahertz Sci Technol., Sep. 30, 2011, vol. 1, No. 1, pp. 201-219 [Retrieved on 2019-0-19] <DOI: 10.1109/TTHZ.2011.2159551> sections IV-VII; fig. 7-8; 18. |
| Taylor, Zachary D., et al. "THz and mm-wave sensing of corneal tissue water content: in vivo sensing and imaging results." IEEE transactions on terahertz science and technology 5.2 (2015): 184-196. (Year: 2011). * |
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| Yoon et al., "Stiffness measurement using terahertz and acoustic waves for biological samples," Optics Express, Dec. 10, 2015, vol. 23, No. 25, pp. 32671-32678 [Retrieved on Aug. 19, 2019] <DOI: 10.1364/OE.23.032671> fig. 1-2; sections 1-2. |
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| Publication number | Publication date |
|---|---|
| SG11202100380PA (en) | 2021-02-25 |
| US20210298594A1 (en) | 2021-09-30 |
| WO2020013762A1 (en) | 2020-01-16 |
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